Until effective insect-selective poisons are discovered, a balance must be established between the need to minimize the adverse environmental impact of insecticides and the need to maximize the survival and health of humans. The long term objective of this proposal is to develop selective insecticides which are toxic to harmful insects but are safe for mammals, birds and fish. The specific aims are to learn more about major neurotransmitter receptors of insects because of their vital regulatory roles for nerve and muscle functions. Discovery of differences between these receptors and their counterparts in vertebrates may be exploited to develop selective insecticides. Three neurotransmitter receptor systems will be investigated: the acetylcholine, glutamate and Gamma-aminobutyric acid receptors of cockroach ganglia and housefly brain and skeletal muscles. The approach used is biochemical and pharmacological. Two major methods are employed to identify the receptors: One is via their binding sites, utilizing binding assays with radiolabeled neurotransmitters or other receptor ligands. The other is via their functions, utilizing measurements of receptor-regulated ion-transport. Interactions of these receptors with insecticides will determine if these vital proteins may be primary or secondary targets for their actions. In addition, interaction of these receptors with neurotoxic agents present in paralytic venoms of wasps and spiders, and with antibiotics produced by entomophagous fungi will be investigated so as to point to novel structures that may be potent insecticides. The emphasis will be on utilization of our biochemical data and others' electrophysiological data to compare neurotransmitter receptors of insects with those of mammals.